The Centennial of the Discovery of Chagas Disease: Facing the Current Challenges

Lannes-Vieira, Joseli; Araújo-Jorge, Tânia C.; Soeiro, Maria de Nazaré Correia; Gadelha, Paulo; Corrêa-Oliveira, Rodrigo

doi:10.1371/journal.pntd.0000645

Cited by 27 publications

(30 citation statements)

References 27 publications

(40 reference statements)

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“…[2][3][4]. A long-lasting chronic phase follows a short acute phase and an asymptomatic indeterminate stage ( Figure 1).…”

Section: Clinical Featuresmentioning

confidence: 99%

“…[2][3][4][5] All these characteristic dysregulations are related to TGF-β-mediated effects. TGF-β plays an important role in both physiological and pathological heart and vascular development.…”

Section: Review Implication Of Tgf-β In Cardiac Complications Of Chagmentioning

confidence: 99%

“…Atrioventricular block is one of the most important signs and a frequent indication for pacemaker implantation in patients with chronic Chagas disease. [2][3][4] Monitoring conduction disturbances through electrocardiography plays a key role in the overall knowledge of Chagas disease, not only because of its importance in longitudinal and epidemiological studies but also because of its diagnostic value, its simplicity and low cost, its sensitivity, and its utility in prognostic evaluation. Patients with slight abnormalities in electrocardiography correspond to an intermediate level of severity of the disease; combined electrocardiography abnormalities generally correlate with greater myocardial compromise.…”

Section: Review Implication Of Tgf-β In Cardiac Complications Of Chagmentioning

confidence: 99%

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The TGF-β Pathway as an Emerging Target for Chagas Disease Therapy

Bailly

et al. 2012

Clin Pharmacol Ther

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Transforming growth factor-β (TGF-β) influences the development of myocardiopathy in Chagas disease through regulation of (i) parasite invasion of heart cells, (ii) an intracellular parasite cycle, (iii) inflammation and immune response, (iv) heart fibrosis and remodeling, and (v) gap junction modulation and heart conduction. In this review, we discuss the rationale for developing TGF-β signaling-interfering therapies as adjuvant approaches for the management of the cardiac alterations of Chagas disease-affected patients.

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“…[2][3][4]. A long-lasting chronic phase follows a short acute phase and an asymptomatic indeterminate stage ( Figure 1).…”

Section: Clinical Featuresmentioning

confidence: 99%

Section: Review Implication Of Tgf-β In Cardiac Complications Of Chagmentioning

confidence: 99%

Section: Review Implication Of Tgf-β In Cardiac Complications Of Chagmentioning

confidence: 99%

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The TGF-β Pathway as an Emerging Target for Chagas Disease Therapy

Bailly

et al. 2012

Clin Pharmacol Ther

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“…ven 100 years after it was first reported (1), Chagas disease remains a serious public health problem in Latin America, with a high social and economic burden (2,3). Moreover, the prevalence of Chagas disease is increasing, mainly due to migration, in countries where it is not endemic, such as the United States and European countries (4)(5)(6)(7).…”

mentioning

confidence: 99%

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Silva

Mediano

Brasil

et al. 2014

Antimicrob Agents Chemother

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Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN. E ven 100 years after it was first reported (1), Chagas disease remains a serious public health problem in Latin America, with a high social and economic burden (2, 3). Moreover, the prevalence of Chagas disease is increasing, mainly due to migration, in countries where it is not endemic, such as the United States and European countries (4-7).Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease (8, 9), and the parasitological cure rate when patients are treated with BZN during the acute phase of the disease is almost 80% (10, 11). Although BZN effectiveness during the chronic phase of the disease remains uncertain (12)(13)(14), there is compelling evidence supporting the beneficial use of BZN even during the chronic phase of Chagas disease (13, 15), and some international guidelines are now advocating the use of BZN even among adults with chronic disease (16-18). However, adverse drug reactions (ADRs) occur in 30% to 87% of the patients treated with BZN (19-21), and 12% to 29% of patients fail to complete their full course of treatment (19-21). Therefore, the development of tools to identify patients with high probabilities of developing ADRs to BZN is highly desirable, as this strategy would improve compliance to BZN treatment and minimize complications (21,22).Logistic regression (LR) is a method often used to predict outcomes in health studies (23,24), and...

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“…Esta enfermedad es un problema importante de salud pública en Centroamérica y Suramérica; actualmente se estima que entre 8 y 15 millones de personas están infectadas con este parásito y cerca de 28 millones se encuentran en riesgo de adquirir la infección (1). Hasta el momento, no existen vacunas disponibles y los fármacos en uso, nifurtimox y beznidazol, presentan poca eficacia para el tratamiento de la fase crónica de la enfermedad y graves efectos colaterales.…”

Section: Introductionunclassified

Expresión diferencial entre estadios de Trypanosoma cruzi I en el aislamiento de un paciente con cardiomiopatía chagásica crónica de zona endémica de Santander, Colombia

2011

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Introducción. Trypanosoma cruzi es el agente causal de la enfermedad de Chagas. Durante la infección en los huéspedes mamíferos, se observan dos formas del parásito: tripomastigotes y amastigotes. En el curso de la diferenciación del parásito cada estadio expresa un patrón de proteínas específicas de fase, las cuales son responsables de sus características morfológicas, bioquímicas y biológicas, que podrían estar determinando un papel importante en la capacidad infecciosa, virulencia y supervivencia del parásito. Objetivo. Analizar la expresión diferencial entre los estadios tripomastigote y amastigote de un aislamiento de T. cruzi I, utilizando la electroforesis en dos dimensiones y la identificación de las proteínas diferencialmente expresadas mediante espectrometría de masas. Materiales y métodos. Se utilizó un clon del aislamiento MHOM/07/338 de T. cruzi I y, mediante electroforesis en dos dimensiones, se compararon los perfiles proteicos de los estadios tripomastigote y amastigote del parásito. Las imágenes se analizaron con el software PDQuest y las proteínas diferencialmente expresadas se identificaron por MALDI TOF o LC MS/MS. Resultados. Los geles bidimensionales mostraron un promedio de 325 manchas proteicas en cada estadio. En los análisis comparativos se detectaron 21 manchas "sobreexpresadas" en el estadio tripomastigote y 30, en el estadio amastigote. Se seleccionaron 16 proteínas para identificación por espectrometría de masas y se clasificaron en diferentes categorías funcionales. Conclusiones. Las proteínas exclusivas de T. cruzi relacionadas, principalmente, con metabolismo glucolítico y ensamble del citoesqueleto, fueron las que presentaron una mayor expresión diferencial entre los estadios tripomastigote y amastigote del parásito. Estas proteínas podrían ser utilizadas para el diseño de fármacos.Palabras clave: Trypanosoma cruzi, enfermedad de Chagas, proteómica, cardiomiopatía chagásica, Colombia. Differential protein expression in developmental stages of Trypanosoma cruzi I isolated from a patient with chronic chagasic cardiomyopathyIntroduction. Trypanosoma cruzi is the causative agent of Chagas disease. During infection in mammalian hosts, two main forms of the parasite are observed: trypomastigotes and amastigotes. During differentiation, each stage of the parasite expresses a pattern of proteins specific to each phase---proteins which are responsible for the cell's morphological, biochemical and biological properties. These properties ultimately govern the infectivity, virulence and survival of the parasite. Objective. A differential expression analysis was conducted to compare trypomastigote and amastigote stages of T. cruzi I isolate, and to identify proteins differentially expressed by means of mass spectrometry. Materials and methods. A T. cruzi clone of the strain MHOM/07/338 was used to analyze the differential expression between trypomastigote stages of a T. cruzi isolate, using two-dimensional electrophoresis and identification of diferentially expressed proteins by mass spectro...

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The Centennial of the Discovery of Chagas Disease: Facing the Current Challenges

Cited by 27 publications

References 27 publications

The TGF-β Pathway as an Emerging Target for Chagas Disease Therapy

The TGF-β Pathway as an Emerging Target for Chagas Disease Therapy

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Expresión diferencial entre estadios de Trypanosoma cruzi I en el aislamiento de un paciente con cardiomiopatía chagásica crónica de zona endémica de Santander, Colombia

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